Adjuvant hormonal therapy is a critical part of routine cancer care for hormonal receptor positive breast cancers;reducing recurrence and mortality by 26 percent and 50 percent, respectively. However, adherence to hormonal therapy has been identified as a significant problem with rates as low as 50 percent. Such non-adherence has been linked to poor outcomes. Little is known about factors that explain reasons for patients'non-adherence since most studies have not prospectively collected detailed data regarding healthcare delivery or psychosocial factors. We have assembled an outstanding team of investigators to fill these gaps. The overall goal of this study is to contribute to the reduction of potential avoidable breast cancer mortality. Guided by the Adherence Model, we will conduct a longitudinal prospective cohort study of 900 Black and White women with hormonal positive breast cancer who initiate therapy and follow them for three years. We will use electronic pharmacy data to capture how long women remain on therapy before they stop treatment. After a baseline interview, we will conduct follow-up interviews at 12, 24, and 36 months to capture changes in side effects and the emergence of new co-morbidities. Detailed data from patient interviews will be merged with electronic medical records and healthcare utilization data. Study aims are to: 1) Evaluate the contribution of clinical, healthcare delivery and psychosocial predictors of adherence;and 2) Determine if predictors identified in Aim 1 moderate and/or mediate relationships between race and adherence. In an exploratory aim we will evaluate whether CYP2D6 polymorphisms are associated with side-effects among women on Tamoxifen, and if so, determine effect size estimates for future research. We will also explore if there are racial differences in sample provision that could affect conclusions. Results from this study have the potential to fill gaps in knowledge regarding reasons for non-adherence to adjuvant hormonal therapy in both Black and White women. Data will be used to inform delivery of hormonal therapy in clinical practice, identify subgroups of patients most at risk for non- adherence, and develop behavioral interventions. Results will be broadly transportable to women with hormonal receptor positive breast cancers which account for the majority of breast cancer cases. PUBLIC HEALTH RELEVANCE: The survival benefits of adjuvant hormonal therapy for women with hormonal receptor positive breast cancers are well documented. However, half of all breast cancer patients who start hormonal therapy discontinue treatment by the fifth year. Non-adherence to therapy has been shown to significantly increase mortality in breast cancer patients. Despite its importance, little is known about factors that explain why so many women fail to complete therapy. In this study, women who start hormonal therapy will be followed for 3 years of treatment to identify clinical, psychosocial, and healthcare delivery factors that predict their adherence. Because little information is known about ethnic differences in adherence to hormonal therapy, we will examine whether the predictors are similar in Black and White women. We will also explore the influence of pharmacogenetic factors and side effects. Study findings will be used to identify women most at risk for stopping treatment and to develop interventions to help women remain on therapy.